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Empagliflozin and cardiovascular outcomes in people with HFrEF

Results from the EMPEROR-Reduced clinical trial, presented at the European Society of Cardiology (ESC) 2020 Congress and published simultaneously in the New England Journal of Medicine, show that the SGLT2 inhibitor empagliflozin significantly improves outcomes in people with heart failure with reduced ejection fraction (HRrEF), with or without diabetes.

In the study, people with class II–IV chronic heart failure and a left ventricular ejection fraction of ≤40% were randomised to empagliflozin 10 mg or placebo, in conjunction with their usual heart failure care. Half of the participants had type 2 diabetes, and outcomes did not differ between those with and without diabetes. After a median follow-up of 16 months, the primary composite outcome of death from cardiovascular causes or hospitalisation for heart failure (HHF) occurred in 19.4% of the empagliflozin group and 24.7% of the placebo group (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.65–0.86).

The reduction in the primary outcome was primarily driven by a reduction in HHF (HR, 0.70; 95% CI, 0.58–0.85), while the observed reduction in cardiovascular death was not significant. A composite renal outcome was also reduced in the empagliflozin group (HR, 0.50; 95% CI, 0.32–0.77).

These results are similar to those from the DAPA-HF trial of dapagliflozin, and suggest a class effect for SGLT2 inhibitors in improving outcomes in those with HFrEF. In addition, EMPEROR-Reduced, which enrolled more people with severe left ventricular dysfunction than DAPA-HF, suggests a role for SGLT2 inhibitors in treating people with more advanced but stable heart failure.

Commenting on the findings at the ESC Congress, lead author Milton Packer (Baylor Heart and Vascular Institute, Dallas, TX, USA) said that these two studies establish SGLT2 inhibitors as a fourth cornerstone in the treatment of heart failure (along with angiotensin receptor-neprilysin inhibitors, beta-blockers and mineralocorticoid receptor antagonists). He stated his belief that people with HFrEF should initiate all four drugs in quick succession within 4–6 weeks of diagnosis.

Click here to read the study results in full.

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